Senile macular degeneration, an aging/degenerative change in the Retinal Pigment Epithelium (RPE) is rapidly becoming one of the major causes of blindness in the United States. One of the more striking and consistent findings in aging postmitotic cells is the intracellular accumulation of lipofuscin. Lipofuscin granules contain lipid and protein and may form in phagosomes (or autophagosomes) as the result of lipid peroxidation of unsaturated lipids of membranes. Lipids may cross-link with each other and with denatured proteins, resulting in material that the cell may not be able to dispose of. These residual bodies (lipofuscin) may then impair cell function by mechanically and metabolically interfering with the structure/function of the cell. In the current proposal the accumulation of lipofuscin in the RPE with age and its topographical distribution will be measured, using microspectrophotometric techniques. These measurements will also be carried out in eyes with known RPE disease in an attempt to determine whether there is a critical level of lipofuscin above which cell death occurs. Preliminary studies suggest that lipofuscin accumulation is related to the overlying rod concentration. Comparative studies will be made in animals with all cone or all rod retinas in an attempt to further understand this relationship. Finally, studies on the experimental modification of the lipofuscin content of RPE cells will be performed. Included will be an evaluation of the effect of light on the RPE. It is hoped that the results of these studies will be useful in retarding or reversing the changes we associate with senile macular degeneration.